A study by CUHK confirms that plasma EBV DNA analysis is useful for screening early asymptomatic NPC. Featured are (right) Professor Dennis Lo and Professor Allen Chan.

A study by the Chinese University of Hong Kong (CUHK) has confirmed the viability of plasma Epstein-Barr virus (EBV) DNA analysis as a screening modality for early stages of nasopharyngeal cancer (NPC). By detecting NPC at its earlier stages, the chances of cure are significantly higher, especially pertaining to individuals of South Chinese descent, who conferred a higher epidemiological risk of developing NPC.

This landmark study, led by Professor Allen Chan and Professor Dennis Lo, was published in the New England Journal of Medicine on 10 August.

A ground-breaking technology to detect NPC

While NPC may be rare in the West, it is a common type of cancer in Hong Kong and Southern China—with more than 800 new cases diagnosed in Hong Kong every year.

NPC remains to be an illusive malignancy due to its often asymptomatic and only presenting in the more advanced stages of the disease. Advanced NPC is not only tougher to treat but, more aggressive, metastasising to other organs of the body via the lymph nodes. While there is no concrete causative agent for NPC—it is closely associated with EBV infection. This served as the background of the landmark research, which CUHK successfully carried out.

Research team of the plasma DNA screening study of nasopharyngeal cancer. Photo credit: CUHK

Between the year 2013 and 2016, the team of researchers screened more than 20,000 middle-aged Chinese men, who were asymptomatic for NPC, using plasma EBV DNA analysis. The blood test managed to flag out 309 participants with persistently positive results, who were then invited for further diagnostic investigations involving nasal endoscopic examination and magnetic resonance imaging (MRI). Of the 300 participants who agreed, 34 were diagnosed as having NPC.

The results of these findings were further bolstered, where three patients who had positive plasma EBV DNA results—but, showed no findings on nasal endoscopic examination—were found to have very early stages of the disease as shown by MRI. In addition, a participant who screened positive—but declined further investigation—was subsequently diagnosed with advanced-stage NPC at 32 months after enrolment to the study; and died two months later.

The ability for the plasma EBV DNA blood test to pick out NPC at an early stage was particularly outstanding—as it provided diagnosed patients with a significant increased chance of curation and survival.

Comparing to the historical cohort in Hong Kong, the new test was proved to be three times (22% vs. 71%) more likely in detecting early stages of NPC. Moreover, patients undergoing treatment following plasma EBV DNA analysis screening had a significantly increased survival rate (3-year progression-free survival, 97% vs. 70%); likely attributed to the early detection and treatment.

Plasma EBV DNA Analysis expected to be available to the public in three years

“This study suggests non-invasive DNA screening strategy could potentially result in better outcomes for patients with NPC. The patients identified by screening were at significantly earlier stages. They could receive more timely and effective treatments, which may improve the progression-free survival and reduce treatment-associated morbidity,” elaborated Chan, Professor at the Department of Chemical Pathology.

In addition, the results of this study reveal significant clinical implications in screening for NPC in the early stages—an area not previously addressed to much success. With the test's ability to detect NPC earlier and more accurately than before—this new test has the potential to be integrated as part of the public health screening for malignancies.

Prof. Dennis Lo (2nd left) remarks that even small NPC tumors can release sufficient amounts of DNA into the blood to allow sensitive detection of very early cancers. Photo credit: CUHK

“This study has demonstrated the potential of circulating DNA analysis for screening early NPC. Even small tumours could release sufficient amounts of tumour DNA into the blood to allow sensitive detection of very early cancers,” expressed Lo, Director of the Li Ka Shing Institute of Health Sciences at CUHK.

Besides the ability to detect small tumours, the plasma EBV DNA analysis can be carried out at a reasonable price point, with the research team hoping to roll out the test to the public market within the next three years.

Commenting on the viability of the plasma EBV DNA analysis in the public market, Lo added, “Considering the shift in stage distribution and potential for significant improvement in mortality and morbidity, NPC screening with EBV DNA analysis appears to be a feasible practice in regions with high incidence.” MIMS

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